US20100098590A1 - Cleaning device, method for detecting suction nozzle clogging, and automatic analyzer - Google Patents
Cleaning device, method for detecting suction nozzle clogging, and automatic analyzer Download PDFInfo
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- US20100098590A1 US20100098590A1 US12/641,193 US64119309A US2010098590A1 US 20100098590 A1 US20100098590 A1 US 20100098590A1 US 64119309 A US64119309 A US 64119309A US 2010098590 A1 US2010098590 A1 US 2010098590A1
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- Prior art keywords
- suction nozzle
- cleaning
- liquid
- nozzle
- reaction
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L13/00—Cleaning or rinsing apparatus
- B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
- G01N2035/1018—Detecting inhomogeneities, e.g. foam, bubbles, clots
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1004—Cleaning sample transfer devices
Definitions
- the present invention relates to a cleaning device, a method for detecting suction nozzle clogging, and an automatic analyzer.
- a conventional automatic analyzer includes a cleaning device that sucks reaction liquid, which is obtained through a reaction between a specimen and a reagent, from a reaction vessel and discharges cleaning liquid into the reaction vessel to clean the reaction vessel (for example, see Japanese Patent Application Laid-open No. 2000-266763).
- the cleaning device sucks the reaction liquid from the reaction vessel using a nozzle, and sometimes a foreign material in the reaction liquid clogs the nozzle.
- a cleaning device includes a discharge nozzle that discharges cleaning liquid; a suction nozzle that is inserted into a cleaning tank or a reaction vessel along with the discharge nozzle to suck the cleaning liquid or reaction liquid in the cleaning tank or the reaction vessel; a discard vessel that is connected to the suction nozzle via a pipe to discard the cleaning liquid or the reaction liquid; a detecting unit that detects whether an electrostatic capacity at least between the suction nozzle and an electrode provided in a middle of the pipe exceeds a predetermined threshold value; a determination unit that determines that the suction nozzle is clogged when a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset clogging determination time, is longer than a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset normal determination time; and a control unit that stops the discharge nozzle from discharging the cleaning liquid to the reaction vessel when the determination unit determines that the suction nozzle is clogged.
- a method for detecting suction nozzle clogging in a cleaning device having a discharge nozzle that discharges cleaning liquid, a suction nozzle that is inserted into a cleaning tank or a reaction vessel along with the discharge nozzle to suck cleaning liquid or reaction liquid in the cleaning tank or the reaction vessel, and a discard vessel that is connected to the suction nozzle via a pipe to discard the cleaning liquid or the reaction liquid
- the method including detecting whether an electrostatic capacity at least between the suction nozzle and an electrode provided in a middle of the pipe exceeds a predetermined threshold value; and determining that the suction nozzle is clogged when a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset clogging determination time, is longer than a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset normal determination time.
- an automatic analyzer that stirs a specimen and a reagent to cause a reaction, measures an optical characteristic of reaction liquid, and analyzes the reaction liquid, the automatic analyzer cleaning a suction nozzle that sucks cleaning liquid or the reaction liquid using the cleaning device
- FIG. 1 is a schematic diagram illustrating the configuration of an automatic analyzer according to an embodiment of the present invention
- FIG. 2 is a schematic explanation diagram illustrating the schematic configuration of a cleaning device
- FIG. 3 is a block diagram illustrating a detecting unit of the cleaning device
- FIG. 4 is a block diagram illustrating a determination control unit of the cleaning device
- FIG. 5 is a diagram illustrating an example of a time chart, in which one cleaning period contains B/F cleaning in a reaction vessel and suction-nozzle cleaning in a cleaning tank;
- FIG. 6 is a schematic diagram illustrating the arrangement of a cleaning tank, a suction nozzle, a pipe, a detection electrode, and a reservoir and illustrating a state where B/F cleaning liquid is sucked between the suction nozzle and the reservoir;
- FIG. 7 is a diagram illustrating a state where the B/F cleaning liquid is further sucked from a position illustrated in FIG. 6 , the leading end of the B/F cleaning liquid comes in contact with the detection electrode, and the suction nozzle and the detection electrode are connected to each other;
- FIG. 8 is a diagram illustrating a state where the sucked B/F cleaning liquid is further sucked from a position illustrated in FIG. 7 and the leading end of the B/F cleaning liquid moves to a position between the detection electrode and the reservoir;
- FIG. 9 is a diagram illustrating a state where the sucked B/F cleaning liquid is further sucked from a position illustrated in FIG. 8 , the leading end of the B/F cleaning liquid comes in contact with the electrode of the reservoir, and the detection electrode and the electrode of the reservoir are connected to each other;
- FIG. 10 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is not clogged;
- FIG. 11 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is partially clogged;
- FIG. 12 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is perfectly clogged;
- FIG. 13 is a flowchart explaining a method for detecting suction nozzle clogging that is performed in the cleaning device
- FIG. 14 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the detection electrode when the suction nozzle is not clogged;
- FIG. 15 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity in the same interval as that of FIG. 14 when the suction nozzle is partially clogged.
- an immune measurement using a heterogeneous reaction is performed.
- an immune reaction (antigen-antibody reaction) is first caused by mixing a specimen and a solid phase that is sensitized by an antibody that specifically couples to a predetermined antigen in the specimen.
- a reaction vessel is applied as a solid phase. It is assumed that a predetermined antibody is previously adsorbed in the vicinity of the inner-wall bottom surface of the reaction vessel.
- reaction liquid within the reaction vessel is sucked by a suction nozzle, B/F cleaning of the reaction vessel (pre-B/F cleaning) is performed by predetermined B/F cleaning liquid discharged from a discharge nozzle, and then an antibody or a specimen component (including an antigen), which is not specifically coupled to the antibody and is isolated from the antibody, is separated and removed from the solid phase. Then, the suction nozzle moves to a cleaning tank along with the discharge nozzle to be cleaned.
- chromogenic substrate in which enzyme that is labeled substance shows activity, is added. A chromogenic reaction is caused between labeled substance remaining in the reaction vessel and the chromogenic substrate. A chromogenic amount is optically measured.
- an antigen concentration in the specimen which is an analysis target, is obtained by performing a comparison between data obtained by the measurement and data (calibration curve) obtained from a normal specimen of which the concentration of an antigen is known.
- operations of the immune reaction, B/F cleaning, and nozzle cleaning are performed plural times.
- concentration of a predetermined antibody in a specimen can be measured.
- an antigen that specifically couples to the antibody is previously adsorbed on a solid phase.
- An analysis of specimen can be performed by applying an immunoassay method using a heterogeneous reaction other than an enzyme immunoassay described above.
- Such an immunoassay method includes a fluorescent immunoassay (FIA) that uses a fluorescent substance as a labeled substance, a radioactive immunoassay (RIA) that uses a radioactive isotope as a labeled substance, a chemical enzyme immunoassay (CLIA) that uses a chemiluminescent substrate as a labeled substance, and a spin reagent immunoassay (SIA) that uses a spin reagent as a labeled substance.
- FFA fluorescent immunoassay
- RIA radioactive immunoassay
- CLIA chemical enzyme immunoassay
- SIA spin reagent immunoassay
- FIG. 1 is a schematic diagram illustrating the main configuration of an automatic analyzer according to an embodiment of the present invention.
- An automatic analyzer 1 includes a measurement system 2 and a control analysis system 40 .
- the measurement system 2 dispenses a sample, such as a specimen, and a reagent to a reaction vessel and performs optical measurement on liquid within the reaction vessel.
- the control analysis system 40 performs driving control on the measurement system 2 and performs an immunological analysis on a sample component based on the measurement result performed by the measurement system 2 .
- These two systems cooperate to perform an immunological analysis on a plurality of sample components automatically and continuously.
- the following explanation is made assuming that the automatic analyzer 1 performs immunological measurement using a heterogeneous reaction.
- the measurement system 2 includes a specimen transferring unit 3 , a carrier reagent table 5 , a liquid reagent table 6 , a reaction table 7 , a specimen dispensing unit 8 , a carrier reagent dispensing unit 9 , a liquid reagent dispensing unit 10 , a stirring unit 13 , a photometry unit 14 , and a cleaning device 20 .
- the specimen transferring unit 3 mounts thereon a plurality of racks 4 , each of which holds specimen vessels 4 a for accommodating specimens, and sequentially transfers the plurality of racks 4 .
- the carrier reagent table 5 holds a plurality of carrier reagent vessels 5 a arranged in a circumferential direction and has a driving unit for rotating it in a circumferential direction.
- the carrier reagent vessel 5 a accommodates a carrier reagent that is used for an antigen-antibody reaction with a specimen.
- the liquid reagent table 6 holds liquid reagent vessels 6 a that accommodate various types of liquid reagents.
- the liquid reagent table 6 has a driving unit for rotating it in a circumferential direction, which is different from the driving unit of the carrier reagent table 5 .
- the reaction table 7 holds reaction vessels 7 a , in which reactions between specimens and reagents are caused, and has a driving unit for rotating it in a circumferential direction similarly to the carrier reagent table 5 .
- each table is kept constant.
- the liquid reagent table 6 is set to a temperature lower than a room temperature to suppress the degradation and denaturation of a reagent.
- the reaction table 7 is set to a temperature equal to a human body temperature.
- the specimen dispensing unit 8 dispenses specimens accommodated in the specimen vessels 4 a on the specimen transferring unit 3 to the reaction vessels 7 a held on the reaction table 7 .
- the carrier reagent dispensing unit 9 dispenses carrier reagents accommodated in the carrier reagent vessels 5 a on the carrier reagent table 5 to the reaction vessels 7 a .
- the liquid reagent dispensing unit 10 dispenses liquid reagents accommodated in the liquid reagent vessels 6 a on the liquid reagent table 6 to the reaction vessels 7 a.
- the specimen vessel 4 a includes an information code recording medium (not shown) affixed thereto that records identification information for identifying a specimen accommodated therein by coding the identification information to an information code such as a bar-code or a two-dimensional code.
- the carrier reagent vessel 5 a and the liquid reagent vessel 6 a each include an information code recording medium (not shown) affixed thereto that records identification information for identifying a reagent accommodated therein by coding the identification information to an information code.
- the measurement system 2 includes an information code reading unit CR 1 that reads an information code affixed to the specimen vessel 4 a , an information code reading unit CR 2 that reads an information code affixed to the carrier reagent vessel 5 a , and an information code reading unit CR 3 that reads an information code affixed to the liquid reagent vessel 6 a.
- the specimen dispensing unit 8 , the carrier reagent dispensing unit 9 , and the liquid reagent dispensing unit 10 each include a canalicular probe that performs the suction and discharge of a specimen, an arm that moves the probe up and down in a vertical direction and rotates the probe in a horizontal direction, and a suction/discharge mechanism that uses a suction/discharge syringe or the like.
- a disposable method is employed.
- a removable chip is attached to the leading end of the probe. The chip is exchanged for each dispensing operation.
- the specimen dispensing unit 8 includes, on an operation line thereof, a chip storing unit 8 a for storing unused chips and a chip discarding unit 8 b for discarding used chips.
- a reaction vessel transferring unit 11 transfers the reaction vessel 7 a in order to place the reaction vessel 7 a on the reaction table 7 or to remove the reaction vessel 7 a from the reaction table 7 .
- the reaction vessel transferring unit 11 includes, on an operation line thereof, a reaction vessel storing unit 11 a for storing unused reaction vessels 7 a and a reaction vessel discarding unit 11 b for discarding used reaction vessels 7 a .
- the reaction vessel transferring unit 11 may have any configuration as far as it transfers liquid without spilling the liquid in the reaction vessel 7 a.
- the stirring unit 13 stirs liquid accommodated in the reaction vessel 7 a .
- the photometry unit 14 includes a photomultiplier tube that measures weak light emitted by reaction liquid within the reaction vessel 7 a . In case of measuring fluorescent light that is generated from reaction liquid, the photometry unit 14 may be provided with a light source for irradiating exciting light.
- the cleaning device 20 performs B/F cleaning of a carrier reagent and cleaning of a suction nozzle 21 b as illustrated in FIG. 2 .
- the cleaning device 20 includes a plurality of B/F cleaning nozzle pairs 21 A to 21 F, each of which has as a pair a discharge nozzle 21 a that discharges B/F cleaning liquid and the suction nozzle 21 b that sucks liquid.
- the suction nozzle 21 b is made of metal excellent in electrical conductivity, such as aluminum.
- the lower end of the suction nozzle 21 b is positioned lower than the lower end of the discharge nozzle 21 a .
- Each of the B/F cleaning nozzle pairs 21 A to 21 F is transferred to a nozzle cleaning tank 30 every time B/F cleaning after an immune reaction in the reaction vessel 7 a is completed using a nozzle transferring unit 22 .
- the nozzle transferring unit 22 collectively moves vertically and horizontally and rotates horizontally the B/F cleaning nozzle pairs 21 A to 21 F. Then, the suction nozzle 21 b is cleaned by the B/F cleaning liquid discharged from the discharge nozzle 21 a .
- a control unit 45 controls the vertical movement of the nozzle transferring unit 22 using a top point at a position raised in a vertical direction as an original point.
- the nozzle transferring unit 22 collectively transfers the B/F cleaning nozzle pairs 21 A to 21 F, relative position relationships between the discharge nozzle 21 a and the suction nozzle 21 b of the nozzle pairs are not changed before and after the transfer.
- the nozzle transferring unit 22 is capable of transferring the nozzle pairs individually.
- the discharge nozzles 21 a are connected to a syringe 24 via a common pipe 23 .
- the syringe 24 includes a cylinder 24 a and a piston 24 b .
- B/F cleaning liquid LBF is introduced into the pipe 23 and the cylinder 24 a .
- the operation of the piston 24 b is controlled by a piston driving unit 25 that is controlled by the control unit 45 .
- the syringe 24 is connected to a cleaning liquid vessel 29 that accommodates the B/F cleaning liquid LBF via a pipe 26 .
- An injection valve 27 that controls the flow of the B/F cleaning liquid LBF and a pump 28 that sucks the B/F cleaning liquid LBF from the cleaning liquid vessel 29 are provided in the pipe 26 .
- the injection valve 27 is opened, the B/F cleaning liquid LBF is filled up into the discharge nozzle 21 a , the syringe 24 , the pipes 23 and 26 using the pump 28 , and then the injection valve 27 is closed to terminate the operation of the pump 28 .
- Each of the suction nozzles 21 b of the B/F cleaning nozzle pairs 21 A to 21 F is connected to a reservoir 33 via an individual pipe 31 .
- Each of the suction nozzles 21 b is connected to a frame ground FG of the automatic analyzer 1 .
- Each of the pipes 31 has the same diameter between the suction nozzle 21 b and the reservoir 33 and provided with a detection electrode 32 at a mid point between the suction nozzle 21 b and the reservoir 33 .
- the detection electrode 32 is provided at the position such that an amount of the B/F cleaning liquid existing between the suction nozzle 21 b and the detection electrode 32 is smaller than an amount of the B/F cleaning liquid within the cleaning tank 30 .
- the distance between the suction nozzle 21 b and the detection electrode 32 is set to be equal to or shorter than the distance between the detection electrode 32 and a reservoir electrode 33 a.
- the detection electrode 32 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 between the suction nozzle 21 b and the detection electrode 32 or between the detection electrode 32 and the reservoir electrode 33 a of the reservoir 33 , and outputs an electrical signal corresponding to the change of electrostatic capacity to a detecting unit 36 .
- the reservoir 33 is connected to a vacuum pump, which causes negative pressure in the reservoir 33 , via a pipe that has a suction valve 34 .
- the reservoir 33 is provided with the reservoir electrodes 33 a at locations to which the respective pipes 31 are connected.
- One end of the reservoir electrode 33 a is connected to the B/F cleaning liquid flowing through the pipe 31 and the other end is connected to the frame ground FG of the automatic analyzer 1 .
- the reaction liquid sucked from the reaction vessel 7 a and the B/F cleaning liquid sucked from the nozzle cleaning tank 30 are discharged from the reservoir 33 to an external waste liquid tank 33 b through a pipe that has an exhaust valve 35 .
- the detecting unit 36 detects the change of electrostatic capacity between the suction nozzle 21 b and the reservoir electrode 33 a as a binarized waveform that is a difference relative to a threshold voltage.
- the detecting unit 36 is provided on a detection board 36 a for each of the B/F cleaning nozzle pairs 21 A to 21 F.
- the detecting unit 36 includes an oscillation circuit 36 b , an I-V converting unit 36 c , a filter 36 d , a DC converting unit 36 e , a peak-hold circuit 36 i , a differential amplifier 36 j , and a comparator 36 k.
- the I-V converting unit 36 c converts the change of electrostatic capacity output from the detection electrode 32 provided in the pipe 31 of the suction nozzle 21 b into the change of an alternating voltage using an alternating current signal output from the oscillation circuit 36 b .
- the filter 36 d is a bandpass filter that passes only a signal near oscillating frequency oscillated by the oscillation circuit 36 b and removes noises included in the change of alternating voltage converted by the I-V converting unit 36 c .
- the DC converting unit 36 e converts voltage variation of alternating current signal into voltage variation of direct current that has less ripples using a rectifying device 36 f , a smoothing circuit 36 g , and a long pass filter 36 h.
- the peak-hold circuit 36 i is a circuit that detects whether the B/F cleaning liquid passes the detection electrode 32 with high precision using the change of electrostatic capacity relative to a reference of electrostatic capacity.
- the reference is an electrostatic capacity when the suction nozzle 21 b does not suck the B/F cleaning liquid.
- the peak-hold circuit 36 i holds a direct voltage before the electrostatic capacity is changed as a reference voltage.
- the peak-hold circuit 36 i resets the previous reference voltage saved in the peak-hold circuit 36 i of each of the detecting units 36 and holds the present new direct voltage as a reference voltage when the B/F cleaning liquid is discharged from one of the discharge nozzles 21 a of the B/F cleaning nozzle pairs 21 A to 21 F in the nozzle cleaning tank 30 .
- the control unit 45 that receives a signal output from the piston driving unit 25 inputs a peak-hold reset signal to the peak-hold circuit 36 i.
- the differential amplifier 36 j outputs a voltage variation amount between the reference voltage held in the peak-hold circuit 36 i and the voltage variation of the direct current converted by the DC converting unit 36 e .
- the comparator 36 k compares the voltage variation amount input from the differential amplifier 36 j with a threshold voltage set in a binarization threshold circuit 36 m and outputs a binarized waveform (see FIGS. 10 to 12 , FIG. 14 , and FIG. 15 ) that is a difference between the voltage variation amount and the threshold voltage to a determination control unit 37 via a photo coupler 36 n .
- the binarized threshold value i.e., the threshold voltage is set to an intermediate value between a voltage value when an electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 is largest and a voltage value when the electrostatic capacity is smallest.
- the determination control unit 37 includes a peak-hold-reset output circuit 38 and determination units 39 that are respectively provided for the B/F cleaning nozzle pairs 21 A to 21 F and respectively determine whether the suction nozzles 21 b are clogged.
- the peak-hold-reset output circuit 38 outputs a peak-hold reset signal to the peak-hold circuit 36 i of the detecting unit 36 .
- a timing at which cleaning liquid is discharged to the reaction vessel 7 a is extracted from a driving signal for the syringe 24 and a driving signal for the B/F cleaning nozzle pairs 21 A to 21 F that are output from the piston driving unit 25 and the nozzle transferring unit 22 and are input to the peak-hold-reset output circuit 38 via the control unit 45 .
- the peak-hold reset signal is pulse-shaped.
- the determination unit 39 totalizes binarized waveforms input from the detecting unit 36 and determines whether the suction nozzle 21 b is clogged. As illustrated in FIG. 4 , the determination unit 39 includes a normal-determination-time setting circuit 39 a , a clogging-determination-time setting circuit 39 b , a first timer 39 e , a second timer 39 f , and a comparing circuit 39 g.
- the normal-determination-time setting circuit 39 a sets the starting point and ending point of a normal determination time based on a determination start signal input from a storage unit 44 through an input port 39 p and a set value 1 input through an input port 39 m , and outputs the points to an AND circuit 39 c .
- the ending point of the normal determination time is the starting point of a clogging determination time.
- the AND circuit 39 c extracts ON components of a binarized waveform, which is input from the normal-determination-time setting circuit 39 a , during the normal determination time and outputs the ON components to the first timer 39 e.
- the clogging-determination-time setting circuit 39 b sets the ending point of the clogging determination time based on a set value 2 input from the storage unit 44 through an input port 39 n , and outputs the point to an AND circuit 39 d .
- the AND circuit 39 d extracts ON components of a binarized waveform, which is input from the clogging-determination-time setting circuit 39 b , during the clogging determination time and outputs the ON components to the second timer 39 f.
- the first timer 39 e totalizes the ON components of the binarized waveform, which is input from the AND circuit 39 c , during the normal determination time and outputs a totalizing time T 1 to the comparing circuit 39 g and an output port 39 h .
- the second timer 39 f totalizes the ON components of the clogging determination time having a binarized waveform input from the AND circuit 39 d , and outputs a totalizing time T 2 to the comparing circuit 39 g and an output port 39 i.
- the comparing circuit 39 g compares the totalizing time T 1 and the totalizing time T 2 input from the first timer 39 e and the second timer 39 f . The comparing circuit 39 g then determines that the suction nozzle 21 b is clogged when the totalizing time T 2 is not less than the totalizing time T 1 (T 1 ⁇ T 2 ) and outputs the determination to an output port 39 j.
- the totalizing time T 1 output to the output port 39 h , the totalizing time T 2 output to the output port 39 i , and the determination result of the effect that the suction nozzle 21 b is clogged output to the output port 39 j are output from the output ports to the storage unit 44 .
- a reset signal read from the storage unit 44 by the control unit 45 is input to an input port 39 k.
- the detecting unit 36 and the determination control unit 37 are illustrated separately from the control unit 45 in FIG. 2 .
- the automatic analyzer 1 of the present invention utilizes the control unit 45 as the detecting unit 36 and the determination control unit 37 to be integrated with the control unit 45 .
- FIG. 1 is a diagram only schematically illustrating the components of the measurement system 2 .
- a mutual positional relationship between the components of the measurement system 2 is a design matter to be determined in accordance with a condition such as a rotation mode of the wheel of the reaction table 7 .
- the control analysis system 40 includes an analysis computing unit 41 , an input unit 42 , an output unit 43 , the storage unit 44 , and the control unit 45 .
- the analysis computing unit 41 performs analysis calculation on the measurement result obtained in the measurement system 2 .
- the input unit 42 inputs an actuation instruction signal of the automatic analyzer 1 and information required for the analysis of a specimen.
- the input unit 42 is realized by a keyboard, a mouse, a microphone, and the like.
- the output unit 43 outputs information including an analysis result, and is realized by a display (CRT, liquid crystal, plasma, organic EL, and the like), a printer, a speaker, and the like.
- the storage unit 44 stores therein information including various types of parameters related to the automatic analyzer 1 or the cleaning device 20 in addition to the analysis result.
- the storage unit 44 includes a hard disk that magnetically stores various information and a memory that loads, when the automatic analyzer 1 and the cleaning device 20 perform various types of processes, programs related to the processes from the hard disk and electrically records the programs.
- the control unit 45 reads the set values 1 and 2 for setting the normal determination time and the clogging determination time, the reset signal, and the determination start signal from the storage unit 44 , and outputs these signals to the determination control unit 37 .
- the set values 1 and 2 are set at the time of maintenance of the automatic analyzer 1 and are input to the storage unit 44 .
- the reset signal is a signal for resetting the totalizing time (T 1 ) totalized by the first timer 39 e of the determination unit 39 , the totalizing time (T 2 ) totalized by the second timer 39 f , and the determination result (T 1 ⁇ T 2 ) performed in the comparing circuit 39 g , and is input from the input port 39 k (see FIG. 4 ) to the determination unit 39 .
- the determination start signal is a signal for instructing the determination control unit 37 to start determination.
- the determination start signal is output from the control unit 45 to the determination unit 39 during a period from a time, at which the discharge of the B/F cleaning liquid from the discharge nozzle 21 a to the reaction vessel 7 a has started in response to the start of drive of the piston driving unit 25 , to a time, at which the discharge nozzle 21 a and the suction nozzle 21 b are transferred to the nozzle cleaning tank 30 by the nozzle transferring unit 22 and the B/F cleaning liquid is discharged to the nozzle cleaning tank 30 to start the nozzle cleaning.
- the storage unit 44 may further include an auxiliary storage device that can read information recorded in a recording medium such as a flexible disk, CD-ROM, DVD-ROM, a magnet-optical disk, a PC card, or an xD picture card.
- a recording medium such as a flexible disk, CD-ROM, DVD-ROM, a magnet-optical disk, a PC card, or an xD picture card.
- the control unit 45 controls the automatic analyzer 1 and reads a program stored in the storage unit 44 from the memory to perform analysis calculation using the measurement result in the measurement system 2 , the control of various types of actuations of the automatic analyzer 1 , and the like.
- the analysis computing unit 41 computes an amount of luminescence of the reaction liquid within the reaction vessel 7 a and uses a calibration curve obtained from a normal specimen and an analysis parameter included in the analysis information in addition to the computation result in order to quantitatively calculate the component of reaction liquid.
- the analysis result obtained in this way is output from the output unit 43 and is further stored in the storage unit 44 .
- the cleaning device 20 of the present invention having the above configuration performs vertical movements and horizontal movements of the plurality of B/F cleaning nozzle pairs 21 A to 21 F using the nozzle transferring unit 22 so as to perform the B/F cleaning of the reaction vessel 7 a and internal/external cleaning of the suction nozzle 21 b in the cleaning tank 30 .
- An example of a time chart in which the B/F cleaning in the reaction vessel 7 a and the cleaning of the suction nozzle 21 b in the cleaning tank 30 are performed in one cleaning period is illustrated in FIG. 5 .
- FIG. 5 is a time chart regarding the movement of the nozzle transferring unit 22 that transfers the discharge nozzle 21 a and the suction nozzle 21 b of one of the B/F cleaning nozzle pairs, the discharge of the B/F cleaning liquid performed by the discharge nozzle 21 a , the opening (nozzle cleaning with the sucking of the B/F cleaning liquid performed by the suction nozzle 21 b ) of the suction valve 34 that causes negative pressure in the reservoir 33 , and the opening of the exhaust valve 35 that discharges liquid (reaction liquid and B/F cleaning liquid) within the reservoir 33 .
- FIG. 5 is a time chart regarding the movement of the nozzle transferring unit 22 that transfers the discharge nozzle 21 a and the suction nozzle 21 b of one of the B/F cleaning nozzle pairs, the discharge of the B/F cleaning liquid performed by the discharge nozzle 21 a , the opening (nozzle cleaning with the sucking of the B/F cleaning liquid performed by the suction nozzle 21 b ) of the suction valve 34 that causes negative pressure in the reservoir
- solid lines show a horizontal movement or a vertical movement of one of the B/F cleaning nozzle pairs performed by the nozzle transferring unit 22 , the discharge of the B/F cleaning liquid from the discharge nozzle 21 a , and the opening of the suction valve 34 and the opening of the exhaust valve 35 . Dotted lines show that the nozzle transferring unit 22 does not move. In FIG. 5 , parts that do not have marks for the opening of the suction valve 34 and the exhaust valve 35 indicate that the valves are closed.
- the nozzle transferring unit 22 moves the B/F cleaning nozzle pairs downward at the position of the reaction vessel 7 a from 0 second to 0.5 second and then stops the pairs at a bottom point from 0.5 second to 1.8 second, and then moves the B/F cleaning nozzle pairs upward toward the top point from 1.8 second to 2.2 second and stops the pairs.
- the suction valve 34 is opened from 0 second to 0.4 second to causes negative pressure in the reservoir 33 , and the reaction liquid within the reaction vessel 7 a is sucked into the reservoir 33 by the suction nozzle 21 b .
- the discharge nozzle 21 a discharges the B/F cleaning liquid into the reaction vessel 7 a from 0.7 second to 1.7 second to perform B/F cleaning on the inside of the reaction vessel 7 a .
- the exhaust valve 35 is opened from 1.5 second to 2.0 second, the sucked reaction liquid is discharged from the reservoir 33 , and the B/F cleaning of the reaction vessel 7 a is completed. Because the suction valve 34 is opened from 2.0 second to 3.2 second and causes negative pressure in the reservoir 33 , the suction nozzle 21 b sucks part of the B/F cleaning liquid within the reaction vessel 7 a while being moved upward by the nozzle transferring unit 22 .
- the nozzle transferring unit 22 horizontally moves the B/F cleaning nozzle pairs from 2.2 second to 2.6 second from the position of the reaction vessel 7 a toward the position of the cleaning tank 30 while keeping the pairs at the top point between 2.2 second and 2.7 second.
- the pairs are kept at the position of the cleaning tank 30 up to 5.8 second.
- the nozzle transferring unit 22 then horizontally moves the B/F cleaning nozzle pairs from 5.8 second to 6.2 second from the position of the cleaning tank 30 toward the position of another reaction vessel 7 a and then stops the pairs between 6.2 second and 7.5 second.
- the nozzle transferring unit 22 moves the B/F cleaning nozzle pairs downward from 2.7 second to 3.1 second and then stops the pairs at the bottom point at the position of the cleaning tank 30 between 3.1 second and 5.4 second, and then moves the B/F cleaning nozzle pairs upward from 5.4 second to 5.8 second and then stops the pairs at the top point.
- the nozzle transferring unit 22 stops the B/F cleaning nozzle pairs at the top point between 5.8 second and 6.3 second, and then moves the B/F cleaning nozzle pairs downward from 6.3 second to 7.2 second and stops the pairs at the bottom point up to 7.5 second.
- the discharge nozzle 21 a discharges the B/F cleaning liquid to the cleaning tank 30 from 3.1 second to 4.2 second. With this, the outside of the suction nozzle 21 b is cleaned. Also, the B/F cleaning liquid just discharged from the discharge nozzle 21 a is sucked by the suction nozzle 21 b up to 3.2 second due to the attractive force of the reservoir 33 that is in negative pressure between 2.0 second and 3.2 second. The inside pressure of the reservoir 33 again becomes negative by opening the suction valve 34 from 4.3 second to 5.0 second, and the B/F cleaning liquid within the cleaning tank 30 is sucked to clean the suction nozzle 21 b . Then, the suction valve 34 is opened from 6.3 second to 7.2 second to cause negative pressure in the reservoir 33 and sucks reaction liquid within another reaction vessel 7 a , toward which the move was made between 5.8 second and 6.2 second.
- FIG. 5 illustrates a basic cleaning period of the cleaning device 20 .
- the B/F cleaning of the reaction vessel 7 a and the internal/external cleaning of the suction nozzle 21 b in the cleaning tank 30 can be performed by changing times or combining a plurality of the cleaning period as needed.
- the nozzle transferring unit 22 moves the plurality of B/F cleaning nozzle pairs 21 A to 21 F to the cleaning tank 30 , and the suction nozzle 21 b sucks the B/F cleaning liquid, which has discharged by the discharge nozzle 21 a to the cleaning tank 30 , from the cleaning tank 30 . Then, the B/F cleaning liquid within the cleaning tank 30 sucked by the suction nozzle 21 b is discharged to the reservoir 33 through the pipe 31 . In this way, the suction nozzle 21 b is cleaned by the sucked B/F cleaning liquid.
- the suction nozzle 21 b further sucks the B/F cleaning liquid LBF within the cleaning tank 30 , and the electrostatic capacity becomes small when the leading end of the B/F cleaning liquid LBF within the pipe 31 has passed the detection electrode 32 and the rear end of the B/F cleaning liquid LBF has also passed the suction nozzle 21 b as illustrated in FIG. 8 .
- FIG. 9 when the leading end of the B/F cleaning liquid LBF within the pipe 31 arrives at the reservoir 33 and the rear end side of the B/F cleaning liquid LBF touches the detection electrode 32 , an electrostatic capacity is largely changed again due to the B/F cleaning liquid LBF between the detection electrode 32 and the reservoir electrode 33 a.
- the detecting unit 36 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 as a binarized waveform that is a difference relative to a threshold voltage.
- FIG. 10 illustrates examples of a voltage variation, a threshold voltage, and a binarized waveform output from the differential amplifier 36 j of the detecting unit 36 based on the change of electrostatic capacity when the suction nozzle 21 b is not clogged with foreign materials. The normal determination time and the clogging determination time are also depicted.
- the binarized waveform has ON states at two points. The first ON state is detected when the leading end of the B/F cleaning liquid LBF within the pipe 31 passes the detection electrode 32 as illustrated in FIG. 7 .
- the second ON state is detected when the leading end of the B/F cleaning liquid LBF within the pipe 31 arrives at the reservoir 33 and the rear end side of the B/F cleaning liquid LBF touches the detection electrode 32 as illustrated in FIG. 9 .
- the time for which the binarized waveform has the ON state in the normal determination time illustrated in FIG. 10 is totalized by the first timer 39 e of the determination unit 39 and is referred to as the totalizing time T 1 .
- the normal determination time starts at zero second and its horizontal axis shows a time scale. This is similar in FIGS. 11 and 12 .
- FIGS. 10 to 12 are diagrams when the pipe 31 is not clogged.
- FIG. 11 illustrates examples of a voltage variation, a threshold voltage, and a binarized waveform output from the differential amplifier 36 j of the detecting unit 36 in the normal determination time and the clogging determination time is.
- the binarized waveform becomes an ON state in the clogging determination time after the termination of the normal determination time. Therefore, the time difference ( ⁇ T) is caused between the ON times of the binarized waveform illustrated in FIG. 11 and the binarized waveform illustrated in FIG. 10 .
- the time for the binarized waveform becomes an ON state in the clogging determination time is totalized by the second timer 39 f of the determination unit 39 as the totalizing time T 2 .
- the suction nozzle 21 b is perfectly clogged, because the suction nozzle 21 b cannot suck the B/F cleaning liquid, the B/F cleaning liquid does not flow through the pipe 31 .
- FIG. 12 illustrates examples of the voltage variation, the threshold voltage, and the binarized waveform output from the differential amplifier 36 j of the detecting unit 36 in the normal determination time and the clogging determination time.
- the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 is detected as a binarized waveform, and the presence or absence of the clogging of the suction nozzle 21 b is determined based on the totalizing times T 1 and T 2 of the binarized waveform in the normal determination time and the clogging determination time.
- Step S 100 the cleaning device 20 determines whether nozzle cleaning in the cleaning tank 30 is started. This determination is made using a signal that is input from the piston driving unit 25 , which causes the discharge nozzle 21 a to discharge the B/F cleaning liquid, to the control unit 45 . As a determination result, when the piston driving unit 25 does not operate and the B/F cleaning liquid is not discharged from the discharge nozzle 21 a (Step S 100 : No), the determination of Step S 100 is repeated.
- Step S 100 When the piston driving unit 25 operates and the B/F cleaning liquid is discharged from the discharge nozzle 21 a into the cleaning tank 30 (Step S 100 : Yes), the cleaning device 20 determines whether a determination start signal is input to the determination unit 39 of the determination control unit 37 (Step S 102 ). This determination is made depending on whether the control unit 45 outputs the determination start signal that is read from the storage unit 44 to the determination unit 39 . When the determination start signal is not input to the determination unit 39 (Step S 102 : No), the cleaning device 20 terminates the clogging detection of the suction nozzle 21 b.
- Step S 104 the cleaning device 20 resets the totalizing times T 1 and T 2 (Step S 104 ).
- the reset of the totalizing times T 1 and T 2 is performed by outputting the reset signal read from the storage unit 44 to the determination control unit 37 by the control unit 45 .
- the cleaning device 20 opens the suction valve 34 (Step S 106 ).
- the opening of the suction valve 34 is performed by outputting an opening signal to the suction valve 34 by the control unit 45 . In this way, negative pressure is caused in the reservoir 33 , the B/F cleaning liquid within the cleaning tank 30 is sucked by the suction nozzle 21 b , and the suction nozzle 21 b is cleaned.
- the cleaning device 20 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 as a binarized waveform (Step S 108 ).
- the detection of the binarized waveform is executed by the detecting unit 36 .
- the cleaning device 20 counts the totalizing time T 1 of the detected binarized waveform in the normal determination time (Step S 110 ).
- the count of the totalizing time T 1 is executed by the determination unit 39 to which the binarized waveform is input.
- Step S 118 the cleaning device 20 determines whether the totalizing time T 2 is not less than the totalizing time T 1 (Step S 118 ). This determination is executed by the comparing circuit 39 g of the determination unit 39 . As a determination result, when the totalizing time T 2 is less than the totalizing time T 1 , the B/F cleaning liquid flows through the pipe 31 within the normal determination time and the suction nozzle 21 b is not clogged. Therefore, the cleaning device 20 terminates the clogging detection of the suction nozzle 21 b.
- the cleaning device 20 determines that the suction nozzle 21 b is clogged (Step S 120 ). Therefore, the cleaning device 20 stops discharging the B/F cleaning liquid to the reaction vessel 7 a (Step S 122 ), and terminates the clogging detection of the suction nozzle 21 b . The cleaning device 20 then causes the output unit 43 of the automatic analyzer 1 to display a warning such as the effect that the suction nozzle 21 b is clogged or the requirement of maintenance.
- the cleaning device 20 detects whether the suction nozzle 21 b is clogged based on the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the pipe 31 between the suction nozzle 21 b and the reservoir electrode 33 a of the reservoir 33 .
- the cleaning device 20 may alternatively detect whether the suction nozzle 21 b is clogged based on the change of electrostatic capacity caused by the B/F cleaning liquid flowing through at least one of the pipe 31 between the suction nozzle 21 b and the detection electrode 32 and the pipe 31 between the detection electrode 32 and the reservoir electrode 33 a of the reservoir 33 .
- FIG. 15 illustrates examples of the voltage variation, the threshold voltage, and the binarized waveform output from the differential amplifier 36 j of the detecting unit 36 in the normal determination time and the clogging determination time when the suction nozzle 21 b is partially clogged.
- the voltage variation, the threshold voltage, and the binarized waveform output from the differential amplifier 36 j of the detecting unit 36 in the normal determination time and the clogging determination time are as illustrated FIG. 12 .
- the cleaning device 20 can determine whether the suction nozzle 21 b is clogged by comparing the totalizing time T 1 of the binarized waveform in the normal determination time with the totalizing time T 2 of the binarized waveform in the clogging determination time that are calculated based on the change of electrostatic capacity between the suction nozzle 21 b and the detection electrode 32 . Similarly, the cleaning device 20 can detect whether the suction nozzle 21 b is clogged based on the change of electrostatic capacity between the detection electrode 32 and the reservoir electrode 33 a of the reservoir 33 .
- the cleaning device 20 detects whether the suction nozzle 21 b is clogged based on the change of electrostatic capacity between the suction nozzle 21 b and the reservoir electrode 33 a of the reservoir 33 because the flow of the B/F cleaning liquid can be checked over the entire length of the pipe 31 .
- the cleaning device 20 detects whether the suction nozzle 21 b is clogged based on the change of electrostatic capacity between the suction nozzle 21 b and the detection electrode 32 because the clogging of the suction nozzle 21 b can be quickly detected.
- the cleaning device 20 can detect whether the suction nozzle 21 b is clogged, using the time at which the binarized waveform becomes an ON state in the normal determination time illustrated in FIG. 10 as a standard and measuring the delay of the binarized waveform that is the time difference ( ⁇ T) illustrated in FIG. 11 between the time and the time at which the binarized waveform becomes an ON state in the clogging determination time by the first timer 39 e and the second timer 39 f .
- the occurrence of temporal clogging of the suction nozzle 21 b and the pipe 31 can be known using the length of the measured time difference ( ⁇ T).
- the automatic analyzer 1 can automatically and previously notice the requirement of maintenance related to the B/F cleaning nozzle pairs 21 A to 21 F and the pipe 31 using the control unit 45 .
- the transfer time and stop time of the B/F cleaning nozzle pairs performed by the nozzle transferring unit 22 , the discharge time of the B/F cleaning liquid performed by the discharge nozzle 21 a , and the opening time of the suction valve 34 and the opening time of the exhaust valve 35 can be appropriately changed in accordance with the B/F cleaning situation in the reaction vessel 7 a and the cleaning situation of the suction nozzle 21 b in the cleaning tank 30 .
- a gray zone time may be provided between the normal determination time and the clogging determination time so as to previously notice the maintenance of the B/F cleaning nozzle pairs 21 A to 21 F and the pipe 31 .
- the cleaning device the method for detecting suction nozzle clogging, and the automatic analyzer that are used for an immunological test are described.
- the present invention can be used in the cleaning device, the method for detecting suction nozzle clogging, and the automatic analyzer that are used for a biochemical test or a gene test.
- the configuration of the detecting unit 36 is not limited to that illustrated in FIG. 3 as far as it can detect the change of electrostatic capacity between the suction nozzle 21 b and the reservoir electrode 33 a as a binarized waveform that is the difference relative to a threshold voltage.
- the configuration of the determination control unit 37 is not limited to that illustrated in FIG. 4 as far as it includes the peak-hold-reset output circuit 38 that outputs a peak-hold reset signal to the peak-hold circuit 36 i of the detecting unit 36 and the determination unit 39 that determines whether each of the suction nozzles 21 b is clogged based on the binarized waveform input from the detecting unit 36 .
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Abstract
Description
- This application is a continuation of PCT international application Ser. No. PCT/JP2007/063032 filed on Jun. 28, 2007 which designates the United States, incorporated herein by reference.
- 1. Field of the Invention
- The present invention relates to a cleaning device, a method for detecting suction nozzle clogging, and an automatic analyzer.
- 2. Description of the Related Art
- A conventional automatic analyzer includes a cleaning device that sucks reaction liquid, which is obtained through a reaction between a specimen and a reagent, from a reaction vessel and discharges cleaning liquid into the reaction vessel to clean the reaction vessel (for example, see Japanese Patent Application Laid-open No. 2000-266763). In such an automatic analyzer, the cleaning device sucks the reaction liquid from the reaction vessel using a nozzle, and sometimes a foreign material in the reaction liquid clogs the nozzle.
- A cleaning device according to an aspect of the present invention includes a discharge nozzle that discharges cleaning liquid; a suction nozzle that is inserted into a cleaning tank or a reaction vessel along with the discharge nozzle to suck the cleaning liquid or reaction liquid in the cleaning tank or the reaction vessel; a discard vessel that is connected to the suction nozzle via a pipe to discard the cleaning liquid or the reaction liquid; a detecting unit that detects whether an electrostatic capacity at least between the suction nozzle and an electrode provided in a middle of the pipe exceeds a predetermined threshold value; a determination unit that determines that the suction nozzle is clogged when a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset clogging determination time, is longer than a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset normal determination time; and a control unit that stops the discharge nozzle from discharging the cleaning liquid to the reaction vessel when the determination unit determines that the suction nozzle is clogged.
- According to another aspect of the present invention, there is provided a method for detecting suction nozzle clogging in a cleaning device having a discharge nozzle that discharges cleaning liquid, a suction nozzle that is inserted into a cleaning tank or a reaction vessel along with the discharge nozzle to suck cleaning liquid or reaction liquid in the cleaning tank or the reaction vessel, and a discard vessel that is connected to the suction nozzle via a pipe to discard the cleaning liquid or the reaction liquid, the method including detecting whether an electrostatic capacity at least between the suction nozzle and an electrode provided in a middle of the pipe exceeds a predetermined threshold value; and determining that the suction nozzle is clogged when a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset clogging determination time, is longer than a totalizing time, for which the electrostatic capacity exceeds the predetermined threshold value during a preset normal determination time.
- According to still another aspect of the present invention, there is provided an automatic analyzer that stirs a specimen and a reagent to cause a reaction, measures an optical characteristic of reaction liquid, and analyzes the reaction liquid, the automatic analyzer cleaning a suction nozzle that sucks cleaning liquid or the reaction liquid using the cleaning device
- The above and other features, advantages and technical and industrial significance of this invention will be better understood by reading the following detailed description of presently preferred embodiments of the invention, when considered in connection with the accompanying drawings.
-
FIG. 1 is a schematic diagram illustrating the configuration of an automatic analyzer according to an embodiment of the present invention; -
FIG. 2 is a schematic explanation diagram illustrating the schematic configuration of a cleaning device; -
FIG. 3 is a block diagram illustrating a detecting unit of the cleaning device; -
FIG. 4 is a block diagram illustrating a determination control unit of the cleaning device; -
FIG. 5 is a diagram illustrating an example of a time chart, in which one cleaning period contains B/F cleaning in a reaction vessel and suction-nozzle cleaning in a cleaning tank; -
FIG. 6 is a schematic diagram illustrating the arrangement of a cleaning tank, a suction nozzle, a pipe, a detection electrode, and a reservoir and illustrating a state where B/F cleaning liquid is sucked between the suction nozzle and the reservoir; -
FIG. 7 is a diagram illustrating a state where the B/F cleaning liquid is further sucked from a position illustrated inFIG. 6 , the leading end of the B/F cleaning liquid comes in contact with the detection electrode, and the suction nozzle and the detection electrode are connected to each other; -
FIG. 8 is a diagram illustrating a state where the sucked B/F cleaning liquid is further sucked from a position illustrated inFIG. 7 and the leading end of the B/F cleaning liquid moves to a position between the detection electrode and the reservoir; -
FIG. 9 is a diagram illustrating a state where the sucked B/F cleaning liquid is further sucked from a position illustrated inFIG. 8 , the leading end of the B/F cleaning liquid comes in contact with the electrode of the reservoir, and the detection electrode and the electrode of the reservoir are connected to each other; -
FIG. 10 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is not clogged; -
FIG. 11 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is partially clogged; -
FIG. 12 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the reservoir when the suction nozzle is perfectly clogged; -
FIG. 13 is a flowchart explaining a method for detecting suction nozzle clogging that is performed in the cleaning device; -
FIG. 14 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity caused by cleaning liquid flowing between the suction nozzle and the detection electrode when the suction nozzle is not clogged; and -
FIG. 15 is a diagram illustrating examples of a voltage variation, a threshold voltage, and a binarized waveform detected by the detecting unit on the basis of the change of electrostatic capacity in the same interval as that ofFIG. 14 when the suction nozzle is partially clogged. - Exemplary embodiments of a cleaning device, a method for detecting suction nozzle clogging, and an automatic analyzer will be described below in detail with reference to the accompanying drawings. An automatic analyzer for immune analysis, to which the cleaning device and the method for detecting suction nozzle clogging are applied, will be described.
- <Outline of Immune Analysis Process>
- The outline of an immune analysis process performed by an automatic analyzer according to an embodiment of the present invention is described first. In the present embodiment, an immune measurement using a heterogeneous reaction is performed. As an example, a case of measuring the concentration of a predetermined antigen in a specimen using an enzyme immunoassay (EIA) will be explained. In the immune analysis process, an immune reaction (antigen-antibody reaction) is first caused by mixing a specimen and a solid phase that is sensitized by an antibody that specifically couples to a predetermined antigen in the specimen. In the following description, a reaction vessel is applied as a solid phase. It is assumed that a predetermined antibody is previously adsorbed in the vicinity of the inner-wall bottom surface of the reaction vessel.
- After the immune reaction, reaction liquid within the reaction vessel is sucked by a suction nozzle, B/F cleaning of the reaction vessel (pre-B/F cleaning) is performed by predetermined B/F cleaning liquid discharged from a discharge nozzle, and then an antibody or a specimen component (including an antigen), which is not specifically coupled to the antibody and is isolated from the antibody, is separated and removed from the solid phase. Then, the suction nozzle moves to a cleaning tank along with the discharge nozzle to be cleaned. In the reaction vessel, chromogenic substrate, in which enzyme that is labeled substance shows activity, is added. A chromogenic reaction is caused between labeled substance remaining in the reaction vessel and the chromogenic substrate. A chromogenic amount is optically measured. Then, an antigen concentration in the specimen, which is an analysis target, is obtained by performing a comparison between data obtained by the measurement and data (calibration curve) obtained from a normal specimen of which the concentration of an antigen is known.
- Sometimes, operations of the immune reaction, B/F cleaning, and nozzle cleaning are performed plural times. Similarly to the above, the concentration of a predetermined antibody in a specimen can be measured. In this case, an antigen that specifically couples to the antibody is previously adsorbed on a solid phase. An analysis of specimen can be performed by applying an immunoassay method using a heterogeneous reaction other than an enzyme immunoassay described above. Such an immunoassay method includes a fluorescent immunoassay (FIA) that uses a fluorescent substance as a labeled substance, a radioactive immunoassay (RIA) that uses a radioactive isotope as a labeled substance, a chemical enzyme immunoassay (CLIA) that uses a chemiluminescent substrate as a labeled substance, and a spin reagent immunoassay (SIA) that uses a spin reagent as a labeled substance.
- <Configuration of Automatic Analyzer and Cleaning Device>
-
FIG. 1 is a schematic diagram illustrating the main configuration of an automatic analyzer according to an embodiment of the present invention. Anautomatic analyzer 1 includes ameasurement system 2 and acontrol analysis system 40. Themeasurement system 2 dispenses a sample, such as a specimen, and a reagent to a reaction vessel and performs optical measurement on liquid within the reaction vessel. Thecontrol analysis system 40 performs driving control on themeasurement system 2 and performs an immunological analysis on a sample component based on the measurement result performed by themeasurement system 2. These two systems cooperate to perform an immunological analysis on a plurality of sample components automatically and continuously. The following explanation is made assuming that theautomatic analyzer 1 performs immunological measurement using a heterogeneous reaction. - As illustrated in
FIG. 1 , themeasurement system 2 includes aspecimen transferring unit 3, a carrier reagent table 5, a liquid reagent table 6, a reaction table 7, aspecimen dispensing unit 8, a carrierreagent dispensing unit 9, a liquidreagent dispensing unit 10, astirring unit 13, aphotometry unit 14, and acleaning device 20. - The
specimen transferring unit 3 mounts thereon a plurality ofracks 4, each of which holdsspecimen vessels 4 a for accommodating specimens, and sequentially transfers the plurality ofracks 4. The carrier reagent table 5 holds a plurality ofcarrier reagent vessels 5 a arranged in a circumferential direction and has a driving unit for rotating it in a circumferential direction. Thecarrier reagent vessel 5 a accommodates a carrier reagent that is used for an antigen-antibody reaction with a specimen. The liquid reagent table 6 holdsliquid reagent vessels 6 a that accommodate various types of liquid reagents. The liquid reagent table 6 has a driving unit for rotating it in a circumferential direction, which is different from the driving unit of the carrier reagent table 5. The reaction table 7 holdsreaction vessels 7 a, in which reactions between specimens and reagents are caused, and has a driving unit for rotating it in a circumferential direction similarly to the carrier reagent table 5. - The temperature of each table is kept constant. For example, the liquid reagent table 6 is set to a temperature lower than a room temperature to suppress the degradation and denaturation of a reagent. The reaction table 7 is set to a temperature equal to a human body temperature.
- The
specimen dispensing unit 8 dispenses specimens accommodated in thespecimen vessels 4 a on thespecimen transferring unit 3 to thereaction vessels 7 a held on the reaction table 7. The carrierreagent dispensing unit 9 dispenses carrier reagents accommodated in thecarrier reagent vessels 5 a on the carrier reagent table 5 to thereaction vessels 7 a. The liquidreagent dispensing unit 10 dispenses liquid reagents accommodated in theliquid reagent vessels 6 a on the liquid reagent table 6 to thereaction vessels 7 a. - The
specimen vessel 4 a includes an information code recording medium (not shown) affixed thereto that records identification information for identifying a specimen accommodated therein by coding the identification information to an information code such as a bar-code or a two-dimensional code. Similarly, thecarrier reagent vessel 5 a and theliquid reagent vessel 6 a each include an information code recording medium (not shown) affixed thereto that records identification information for identifying a reagent accommodated therein by coding the identification information to an information code. Themeasurement system 2 includes an information code reading unit CR1 that reads an information code affixed to thespecimen vessel 4 a, an information code reading unit CR2 that reads an information code affixed to thecarrier reagent vessel 5 a, and an information code reading unit CR3 that reads an information code affixed to theliquid reagent vessel 6 a. - The
specimen dispensing unit 8, the carrierreagent dispensing unit 9, and the liquidreagent dispensing unit 10 each include a canalicular probe that performs the suction and discharge of a specimen, an arm that moves the probe up and down in a vertical direction and rotates the probe in a horizontal direction, and a suction/discharge mechanism that uses a suction/discharge syringe or the like. In order to prevent contamination and carry-over, a disposable method is employed. A removable chip is attached to the leading end of the probe. The chip is exchanged for each dispensing operation. Thespecimen dispensing unit 8 includes, on an operation line thereof, achip storing unit 8 a for storing unused chips and achip discarding unit 8 b for discarding used chips. - A reaction
vessel transferring unit 11 transfers thereaction vessel 7 a in order to place thereaction vessel 7 a on the reaction table 7 or to remove thereaction vessel 7 a from the reaction table 7. The reactionvessel transferring unit 11 includes, on an operation line thereof, a reactionvessel storing unit 11 a for storingunused reaction vessels 7 a and a reactionvessel discarding unit 11 b for discarding usedreaction vessels 7 a. The reactionvessel transferring unit 11 may have any configuration as far as it transfers liquid without spilling the liquid in thereaction vessel 7 a. - The stirring
unit 13 stirs liquid accommodated in thereaction vessel 7 a. Thephotometry unit 14 includes a photomultiplier tube that measures weak light emitted by reaction liquid within thereaction vessel 7 a. In case of measuring fluorescent light that is generated from reaction liquid, thephotometry unit 14 may be provided with a light source for irradiating exciting light. - The
cleaning device 20 performs B/F cleaning of a carrier reagent and cleaning of asuction nozzle 21 b as illustrated inFIG. 2 . Thecleaning device 20 includes a plurality of B/Fcleaning nozzle pairs 21A to 21F, each of which has as a pair adischarge nozzle 21 a that discharges B/F cleaning liquid and thesuction nozzle 21 b that sucks liquid. Thesuction nozzle 21 b is made of metal excellent in electrical conductivity, such as aluminum. The lower end of thesuction nozzle 21 b is positioned lower than the lower end of thedischarge nozzle 21 a. Each of the B/Fcleaning nozzle pairs 21A to 21F is transferred to anozzle cleaning tank 30 every time B/F cleaning after an immune reaction in thereaction vessel 7 a is completed using anozzle transferring unit 22. Thenozzle transferring unit 22 collectively moves vertically and horizontally and rotates horizontally the B/Fcleaning nozzle pairs 21A to 21F. Then, thesuction nozzle 21 b is cleaned by the B/F cleaning liquid discharged from thedischarge nozzle 21 a. Acontrol unit 45 controls the vertical movement of thenozzle transferring unit 22 using a top point at a position raised in a vertical direction as an original point. - Because the
nozzle transferring unit 22 collectively transfers the B/Fcleaning nozzle pairs 21A to 21F, relative position relationships between thedischarge nozzle 21 a and thesuction nozzle 21 b of the nozzle pairs are not changed before and after the transfer. Incidentally, thenozzle transferring unit 22 is capable of transferring the nozzle pairs individually. - The discharge nozzles 21 a are connected to a
syringe 24 via acommon pipe 23. Thesyringe 24 includes acylinder 24 a and apiston 24 b. B/F cleaning liquid LBF is introduced into thepipe 23 and thecylinder 24 a. In thesyringe 24, the operation of thepiston 24 b is controlled by apiston driving unit 25 that is controlled by thecontrol unit 45. Thesyringe 24 is connected to a cleaningliquid vessel 29 that accommodates the B/F cleaning liquid LBF via apipe 26. Aninjection valve 27 that controls the flow of the B/F cleaning liquid LBF and apump 28 that sucks the B/F cleaning liquid LBF from the cleaningliquid vessel 29 are provided in thepipe 26. When the B/F cleaning liquid LBF is to be introduced into thepipe 23 and thecylinder 24 a, theinjection valve 27 is opened, the B/F cleaning liquid LBF is filled up into thedischarge nozzle 21 a, thesyringe 24, thepipes pump 28, and then theinjection valve 27 is closed to terminate the operation of thepump 28. - Each of the
suction nozzles 21 b of the B/Fcleaning nozzle pairs 21A to 21F is connected to areservoir 33 via anindividual pipe 31. Each of thesuction nozzles 21 b is connected to a frame ground FG of theautomatic analyzer 1. Each of thepipes 31 has the same diameter between thesuction nozzle 21 b and thereservoir 33 and provided with adetection electrode 32 at a mid point between thesuction nozzle 21 b and thereservoir 33. Thedetection electrode 32 is provided at the position such that an amount of the B/F cleaning liquid existing between thesuction nozzle 21 b and thedetection electrode 32 is smaller than an amount of the B/F cleaning liquid within thecleaning tank 30. The distance between thesuction nozzle 21 b and thedetection electrode 32 is set to be equal to or shorter than the distance between thedetection electrode 32 and areservoir electrode 33 a. - The
detection electrode 32 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 between thesuction nozzle 21 b and thedetection electrode 32 or between thedetection electrode 32 and thereservoir electrode 33 a of thereservoir 33, and outputs an electrical signal corresponding to the change of electrostatic capacity to a detectingunit 36. - The
reservoir 33 is connected to a vacuum pump, which causes negative pressure in thereservoir 33, via a pipe that has asuction valve 34. Thereservoir 33 is provided with thereservoir electrodes 33 a at locations to which therespective pipes 31 are connected. One end of thereservoir electrode 33 a is connected to the B/F cleaning liquid flowing through thepipe 31 and the other end is connected to the frame ground FG of theautomatic analyzer 1. The reaction liquid sucked from thereaction vessel 7 a and the B/F cleaning liquid sucked from thenozzle cleaning tank 30 are discharged from thereservoir 33 to an externalwaste liquid tank 33 b through a pipe that has anexhaust valve 35. - The detecting
unit 36 detects the change of electrostatic capacity between thesuction nozzle 21 b and thereservoir electrode 33 a as a binarized waveform that is a difference relative to a threshold voltage. The detectingunit 36 is provided on adetection board 36 a for each of the B/Fcleaning nozzle pairs 21A to 21F. As illustrated inFIG. 3 , the detectingunit 36 includes anoscillation circuit 36 b, an I-V convertingunit 36 c, afilter 36 d, aDC converting unit 36 e, a peak-hold circuit 36 i, adifferential amplifier 36 j, and acomparator 36 k. - The
I-V converting unit 36 c converts the change of electrostatic capacity output from thedetection electrode 32 provided in thepipe 31 of thesuction nozzle 21 b into the change of an alternating voltage using an alternating current signal output from theoscillation circuit 36 b. Thefilter 36 d is a bandpass filter that passes only a signal near oscillating frequency oscillated by theoscillation circuit 36 b and removes noises included in the change of alternating voltage converted by theI-V converting unit 36 c. TheDC converting unit 36 e converts voltage variation of alternating current signal into voltage variation of direct current that has less ripples using arectifying device 36 f, a smoothingcircuit 36 g, and along pass filter 36 h. - The peak-
hold circuit 36 i is a circuit that detects whether the B/F cleaning liquid passes thedetection electrode 32 with high precision using the change of electrostatic capacity relative to a reference of electrostatic capacity. The reference is an electrostatic capacity when thesuction nozzle 21 b does not suck the B/F cleaning liquid. The peak-hold circuit 36 i holds a direct voltage before the electrostatic capacity is changed as a reference voltage. In order to use a stable electrostatic capacity as a reference, the peak-hold circuit 36 i resets the previous reference voltage saved in the peak-hold circuit 36 i of each of the detectingunits 36 and holds the present new direct voltage as a reference voltage when the B/F cleaning liquid is discharged from one of thedischarge nozzles 21 a of the B/Fcleaning nozzle pairs 21A to 21F in thenozzle cleaning tank 30. At that time, thecontrol unit 45 that receives a signal output from thepiston driving unit 25 inputs a peak-hold reset signal to the peak-hold circuit 36 i. - The
differential amplifier 36 j outputs a voltage variation amount between the reference voltage held in the peak-hold circuit 36 i and the voltage variation of the direct current converted by theDC converting unit 36 e. Thecomparator 36 k compares the voltage variation amount input from thedifferential amplifier 36 j with a threshold voltage set in abinarization threshold circuit 36 m and outputs a binarized waveform (seeFIGS. 10 to 12 ,FIG. 14 , andFIG. 15 ) that is a difference between the voltage variation amount and the threshold voltage to adetermination control unit 37 via aphoto coupler 36 n. The binarized threshold value, i.e., the threshold voltage is set to an intermediate value between a voltage value when an electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 is largest and a voltage value when the electrostatic capacity is smallest. - As illustrated in
FIG. 4 , thedetermination control unit 37 includes a peak-hold-reset output circuit 38 anddetermination units 39 that are respectively provided for the B/Fcleaning nozzle pairs 21A to 21F and respectively determine whether thesuction nozzles 21 b are clogged. - The peak-hold-
reset output circuit 38 outputs a peak-hold reset signal to the peak-hold circuit 36 i of the detectingunit 36. Concerning the peak-hold reset signal, a timing at which cleaning liquid is discharged to thereaction vessel 7 a is extracted from a driving signal for thesyringe 24 and a driving signal for the B/Fcleaning nozzle pairs 21A to 21F that are output from thepiston driving unit 25 and thenozzle transferring unit 22 and are input to the peak-hold-reset output circuit 38 via thecontrol unit 45. The peak-hold reset signal is pulse-shaped. - The
determination unit 39 totalizes binarized waveforms input from the detectingunit 36 and determines whether thesuction nozzle 21 b is clogged. As illustrated inFIG. 4 , thedetermination unit 39 includes a normal-determination-time setting circuit 39 a, a clogging-determination-time setting circuit 39 b, afirst timer 39 e, asecond timer 39 f, and a comparingcircuit 39 g. - The normal-determination-
time setting circuit 39 a sets the starting point and ending point of a normal determination time based on a determination start signal input from astorage unit 44 through aninput port 39 p and aset value 1 input through aninput port 39 m, and outputs the points to an ANDcircuit 39 c. The ending point of the normal determination time is the starting point of a clogging determination time. The ANDcircuit 39 c extracts ON components of a binarized waveform, which is input from the normal-determination-time setting circuit 39 a, during the normal determination time and outputs the ON components to thefirst timer 39 e. - The clogging-determination-
time setting circuit 39 b sets the ending point of the clogging determination time based on aset value 2 input from thestorage unit 44 through aninput port 39 n, and outputs the point to an ANDcircuit 39 d. The ANDcircuit 39 d extracts ON components of a binarized waveform, which is input from the clogging-determination-time setting circuit 39 b, during the clogging determination time and outputs the ON components to thesecond timer 39 f. - The
first timer 39 e totalizes the ON components of the binarized waveform, which is input from the ANDcircuit 39 c, during the normal determination time and outputs a totalizing time T1 to the comparingcircuit 39 g and anoutput port 39 h. Thesecond timer 39 f totalizes the ON components of the clogging determination time having a binarized waveform input from the ANDcircuit 39 d, and outputs a totalizing time T2 to the comparingcircuit 39 g and anoutput port 39 i. - The comparing
circuit 39 g compares the totalizing time T1 and the totalizing time T2 input from thefirst timer 39 e and thesecond timer 39 f. The comparingcircuit 39 g then determines that thesuction nozzle 21 b is clogged when the totalizing time T2 is not less than the totalizing time T1 (T1≦T2) and outputs the determination to anoutput port 39 j. - The totalizing time T1 output to the
output port 39 h, the totalizing time T2 output to theoutput port 39 i, and the determination result of the effect that thesuction nozzle 21 b is clogged output to theoutput port 39 j are output from the output ports to thestorage unit 44. A reset signal read from thestorage unit 44 by thecontrol unit 45 is input to aninput port 39 k. - The detecting
unit 36 and thedetermination control unit 37 are illustrated separately from thecontrol unit 45 inFIG. 2 . However, in order to simplify the configuration, theautomatic analyzer 1 of the present invention utilizes thecontrol unit 45 as the detectingunit 36 and thedetermination control unit 37 to be integrated with thecontrol unit 45. - In the
cleaning device 20 having the above-described configuration and function, operations of thenozzle transferring unit 22, thepiston driving unit 25, theinjection valve 27, thepump 28, thesuction valve 34, and theexhaust valve 35 are controlled by thecontrol unit 45 of thecontrol analysis system 40. - In the
measurement system 2 having the above-described configuration, a rotation angle of the reaction table 7 rotated by one rotation actuation is previously determined. All components are arranged so that dispensing of a specimen or various types of reagents can be performed simultaneously and variously together with this rotation. Thus,FIG. 1 is a diagram only schematically illustrating the components of themeasurement system 2. In other words, a mutual positional relationship between the components of themeasurement system 2 is a design matter to be determined in accordance with a condition such as a rotation mode of the wheel of the reaction table 7. - The
control analysis system 40 includes ananalysis computing unit 41, aninput unit 42, anoutput unit 43, thestorage unit 44, and thecontrol unit 45. - The
analysis computing unit 41 performs analysis calculation on the measurement result obtained in themeasurement system 2. Theinput unit 42 inputs an actuation instruction signal of theautomatic analyzer 1 and information required for the analysis of a specimen. Theinput unit 42 is realized by a keyboard, a mouse, a microphone, and the like. Theoutput unit 43 outputs information including an analysis result, and is realized by a display (CRT, liquid crystal, plasma, organic EL, and the like), a printer, a speaker, and the like. - The
storage unit 44 stores therein information including various types of parameters related to theautomatic analyzer 1 or thecleaning device 20 in addition to the analysis result. Thestorage unit 44 includes a hard disk that magnetically stores various information and a memory that loads, when theautomatic analyzer 1 and thecleaning device 20 perform various types of processes, programs related to the processes from the hard disk and electrically records the programs. During initialization, thecontrol unit 45 reads the set values 1 and 2 for setting the normal determination time and the clogging determination time, the reset signal, and the determination start signal from thestorage unit 44, and outputs these signals to thedetermination control unit 37. The set values 1 and 2 are set at the time of maintenance of theautomatic analyzer 1 and are input to thestorage unit 44. - The reset signal is a signal for resetting the totalizing time (T1) totalized by the
first timer 39 e of thedetermination unit 39, the totalizing time (T2) totalized by thesecond timer 39 f, and the determination result (T1≦T2) performed in the comparingcircuit 39 g, and is input from theinput port 39 k (seeFIG. 4 ) to thedetermination unit 39. The determination start signal is a signal for instructing thedetermination control unit 37 to start determination. The determination start signal is output from thecontrol unit 45 to thedetermination unit 39 during a period from a time, at which the discharge of the B/F cleaning liquid from thedischarge nozzle 21 a to thereaction vessel 7 a has started in response to the start of drive of thepiston driving unit 25, to a time, at which thedischarge nozzle 21 a and thesuction nozzle 21 b are transferred to thenozzle cleaning tank 30 by thenozzle transferring unit 22 and the B/F cleaning liquid is discharged to thenozzle cleaning tank 30 to start the nozzle cleaning. - The
storage unit 44 may further include an auxiliary storage device that can read information recorded in a recording medium such as a flexible disk, CD-ROM, DVD-ROM, a magnet-optical disk, a PC card, or an xD picture card. - The
control unit 45 controls theautomatic analyzer 1 and reads a program stored in thestorage unit 44 from the memory to perform analysis calculation using the measurement result in themeasurement system 2, the control of various types of actuations of theautomatic analyzer 1, and the like. - When the
control analysis system 40 having the above configuration receives a photometric result of weak light emitted by reaction liquid from thephotometry unit 14, theanalysis computing unit 41 computes an amount of luminescence of the reaction liquid within thereaction vessel 7 a and uses a calibration curve obtained from a normal specimen and an analysis parameter included in the analysis information in addition to the computation result in order to quantitatively calculate the component of reaction liquid. The analysis result obtained in this way is output from theoutput unit 43 and is further stored in thestorage unit 44. - The
cleaning device 20 of the present invention having the above configuration performs vertical movements and horizontal movements of the plurality of B/Fcleaning nozzle pairs 21A to 21F using thenozzle transferring unit 22 so as to perform the B/F cleaning of thereaction vessel 7 a and internal/external cleaning of thesuction nozzle 21 b in thecleaning tank 30. An example of a time chart in which the B/F cleaning in thereaction vessel 7 a and the cleaning of thesuction nozzle 21 b in thecleaning tank 30 are performed in one cleaning period is illustrated inFIG. 5 . -
FIG. 5 is a time chart regarding the movement of thenozzle transferring unit 22 that transfers thedischarge nozzle 21 a and thesuction nozzle 21 b of one of the B/F cleaning nozzle pairs, the discharge of the B/F cleaning liquid performed by thedischarge nozzle 21 a, the opening (nozzle cleaning with the sucking of the B/F cleaning liquid performed by thesuction nozzle 21 b) of thesuction valve 34 that causes negative pressure in thereservoir 33, and the opening of theexhaust valve 35 that discharges liquid (reaction liquid and B/F cleaning liquid) within thereservoir 33. InFIG. 5 , solid lines show a horizontal movement or a vertical movement of one of the B/F cleaning nozzle pairs performed by thenozzle transferring unit 22, the discharge of the B/F cleaning liquid from thedischarge nozzle 21 a, and the opening of thesuction valve 34 and the opening of theexhaust valve 35. Dotted lines show that thenozzle transferring unit 22 does not move. InFIG. 5 , parts that do not have marks for the opening of thesuction valve 34 and theexhaust valve 35 indicate that the valves are closed. - As illustrated in
FIG. 5 , in thecleaning device 20, thenozzle transferring unit 22 moves the B/F cleaning nozzle pairs downward at the position of thereaction vessel 7 a from 0 second to 0.5 second and then stops the pairs at a bottom point from 0.5 second to 1.8 second, and then moves the B/F cleaning nozzle pairs upward toward the top point from 1.8 second to 2.2 second and stops the pairs. During that time, thesuction valve 34 is opened from 0 second to 0.4 second to causes negative pressure in thereservoir 33, and the reaction liquid within thereaction vessel 7 a is sucked into thereservoir 33 by thesuction nozzle 21 b. Thedischarge nozzle 21 a discharges the B/F cleaning liquid into thereaction vessel 7 a from 0.7 second to 1.7 second to perform B/F cleaning on the inside of thereaction vessel 7 a. Theexhaust valve 35 is opened from 1.5 second to 2.0 second, the sucked reaction liquid is discharged from thereservoir 33, and the B/F cleaning of thereaction vessel 7 a is completed. Because thesuction valve 34 is opened from 2.0 second to 3.2 second and causes negative pressure in thereservoir 33, thesuction nozzle 21 b sucks part of the B/F cleaning liquid within thereaction vessel 7 a while being moved upward by thenozzle transferring unit 22. - Subsequently, the
nozzle transferring unit 22 horizontally moves the B/F cleaning nozzle pairs from 2.2 second to 2.6 second from the position of thereaction vessel 7 a toward the position of thecleaning tank 30 while keeping the pairs at the top point between 2.2 second and 2.7 second. The pairs are kept at the position of thecleaning tank 30 up to 5.8 second. Thenozzle transferring unit 22 then horizontally moves the B/F cleaning nozzle pairs from 5.8 second to 6.2 second from the position of thecleaning tank 30 toward the position of anotherreaction vessel 7 a and then stops the pairs between 6.2 second and 7.5 second. Thenozzle transferring unit 22 moves the B/F cleaning nozzle pairs downward from 2.7 second to 3.1 second and then stops the pairs at the bottom point at the position of thecleaning tank 30 between 3.1 second and 5.4 second, and then moves the B/F cleaning nozzle pairs upward from 5.4 second to 5.8 second and then stops the pairs at the top point. Thenozzle transferring unit 22 stops the B/F cleaning nozzle pairs at the top point between 5.8 second and 6.3 second, and then moves the B/F cleaning nozzle pairs downward from 6.3 second to 7.2 second and stops the pairs at the bottom point up to 7.5 second. - During that time, the
discharge nozzle 21 a discharges the B/F cleaning liquid to thecleaning tank 30 from 3.1 second to 4.2 second. With this, the outside of thesuction nozzle 21 b is cleaned. Also, the B/F cleaning liquid just discharged from thedischarge nozzle 21 a is sucked by thesuction nozzle 21 b up to 3.2 second due to the attractive force of thereservoir 33 that is in negative pressure between 2.0 second and 3.2 second. The inside pressure of thereservoir 33 again becomes negative by opening thesuction valve 34 from 4.3 second to 5.0 second, and the B/F cleaning liquid within thecleaning tank 30 is sucked to clean thesuction nozzle 21 b. Then, thesuction valve 34 is opened from 6.3 second to 7.2 second to cause negative pressure in thereservoir 33 and sucks reaction liquid within anotherreaction vessel 7 a, toward which the move was made between 5.8 second and 6.2 second. -
FIG. 5 illustrates a basic cleaning period of thecleaning device 20. The B/F cleaning of thereaction vessel 7 a and the internal/external cleaning of thesuction nozzle 21 b in thecleaning tank 30 can be performed by changing times or combining a plurality of the cleaning period as needed. - The
nozzle transferring unit 22 moves the plurality of B/Fcleaning nozzle pairs 21A to 21F to thecleaning tank 30, and thesuction nozzle 21 b sucks the B/F cleaning liquid, which has discharged by thedischarge nozzle 21 a to thecleaning tank 30, from thecleaning tank 30. Then, the B/F cleaning liquid within thecleaning tank 30 sucked by thesuction nozzle 21 b is discharged to thereservoir 33 through thepipe 31. In this way, thesuction nozzle 21 b is cleaned by the sucked B/F cleaning liquid. When thesuction nozzle 21 b sucks the B/F cleaning liquid from thecleaning tank 30, the B/F cleaning liquid LBF within thecleaning tank 30 is sucked into thepipe 31 as illustrated inFIG. 6 . As illustrated inFIG. 7 , when the leading end of the B/F cleaning liquid LBF within thepipe 31 comes in contact with thedetection electrode 32, the electrostatic capacity is largely changed due to the B/F cleaning liquid LBF between thesuction nozzle 21 b and thedetection electrode 32. - The
suction nozzle 21 b further sucks the B/F cleaning liquid LBF within thecleaning tank 30, and the electrostatic capacity becomes small when the leading end of the B/F cleaning liquid LBF within thepipe 31 has passed thedetection electrode 32 and the rear end of the B/F cleaning liquid LBF has also passed thesuction nozzle 21 b as illustrated inFIG. 8 . As illustrated inFIG. 9 , when the leading end of the B/F cleaning liquid LBF within thepipe 31 arrives at thereservoir 33 and the rear end side of the B/F cleaning liquid LBF touches thedetection electrode 32, an electrostatic capacity is largely changed again due to the B/F cleaning liquid LBF between thedetection electrode 32 and thereservoir electrode 33 a. - In the
cleaning device 20, the detectingunit 36 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 as a binarized waveform that is a difference relative to a threshold voltage.FIG. 10 illustrates examples of a voltage variation, a threshold voltage, and a binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 based on the change of electrostatic capacity when thesuction nozzle 21 b is not clogged with foreign materials. The normal determination time and the clogging determination time are also depicted. InFIG. 10 , the binarized waveform has ON states at two points. The first ON state is detected when the leading end of the B/F cleaning liquid LBF within thepipe 31 passes thedetection electrode 32 as illustrated inFIG. 7 . The second ON state is detected when the leading end of the B/F cleaning liquid LBF within thepipe 31 arrives at thereservoir 33 and the rear end side of the B/F cleaning liquid LBF touches thedetection electrode 32 as illustrated inFIG. 9 . The time for which the binarized waveform has the ON state in the normal determination time illustrated inFIG. 10 is totalized by thefirst timer 39 e of thedetermination unit 39 and is referred to as the totalizing time T1. InFIG. 10 , the normal determination time starts at zero second and its horizontal axis shows a time scale. This is similar inFIGS. 11 and 12 .FIGS. 10 to 12 are diagrams when thepipe 31 is not clogged. - When the
suction nozzle 21 b is partially clogged, the flow of the B/F cleaning liquid within thepipe 31 becomes slow.FIG. 11 illustrates examples of a voltage variation, a threshold voltage, and a binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 in the normal determination time and the clogging determination time is. As illustrated inFIG. 11 , because the flow of the B/F cleaning liquid within thepipe 31 is slow, the binarized waveform becomes an ON state in the clogging determination time after the termination of the normal determination time. Therefore, the time difference (ΔT) is caused between the ON times of the binarized waveform illustrated inFIG. 11 and the binarized waveform illustrated inFIG. 10 . The time for the binarized waveform becomes an ON state in the clogging determination time is totalized by thesecond timer 39 f of thedetermination unit 39 as the totalizing time T2. When thesuction nozzle 21 b is perfectly clogged, because thesuction nozzle 21 b cannot suck the B/F cleaning liquid, the B/F cleaning liquid does not flow through thepipe 31.FIG. 12 illustrates examples of the voltage variation, the threshold voltage, and the binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 in the normal determination time and the clogging determination time. - In the method for detecting suction nozzle clogging according to the present invention, the change of electrostatic capacity caused by the B/F cleaning liquid flowing through the
pipe 31 is detected as a binarized waveform, and the presence or absence of the clogging of thesuction nozzle 21 b is determined based on the totalizing times T1 and T2 of the binarized waveform in the normal determination time and the clogging determination time. - Hereinafter, the method for detecting suction nozzle clogging performed in the
cleaning device 20 will be described with reference to the flowchart illustrated inFIG. 13 . - First, when the electric source of the
automatic analyzer 1 is turned on and thecontrol unit 45 is initialized, thecleaning device 20 determines whether nozzle cleaning in thecleaning tank 30 is started (Step S100). This determination is made using a signal that is input from thepiston driving unit 25, which causes thedischarge nozzle 21 a to discharge the B/F cleaning liquid, to thecontrol unit 45. As a determination result, when thepiston driving unit 25 does not operate and the B/F cleaning liquid is not discharged from thedischarge nozzle 21 a (Step S100: No), the determination of Step S100 is repeated. - When the
piston driving unit 25 operates and the B/F cleaning liquid is discharged from thedischarge nozzle 21 a into the cleaning tank 30 (Step S100: Yes), thecleaning device 20 determines whether a determination start signal is input to thedetermination unit 39 of the determination control unit 37 (Step S102). This determination is made depending on whether thecontrol unit 45 outputs the determination start signal that is read from thestorage unit 44 to thedetermination unit 39. When the determination start signal is not input to the determination unit 39 (Step S102: No), thecleaning device 20 terminates the clogging detection of thesuction nozzle 21 b. - In contrast, when the determination start signal is input to the determination unit 39 (Step S102: Yes), the
cleaning device 20 resets the totalizing times T1 and T2 (Step S104). The reset of the totalizing times T1 and T2 is performed by outputting the reset signal read from thestorage unit 44 to thedetermination control unit 37 by thecontrol unit 45. - Subsequently, the
cleaning device 20 opens the suction valve 34 (Step S106). The opening of thesuction valve 34 is performed by outputting an opening signal to thesuction valve 34 by thecontrol unit 45. In this way, negative pressure is caused in thereservoir 33, the B/F cleaning liquid within thecleaning tank 30 is sucked by thesuction nozzle 21 b, and thesuction nozzle 21 b is cleaned. - Subsequently, the
cleaning device 20 detects the change of electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 as a binarized waveform (Step S108). The detection of the binarized waveform is executed by the detectingunit 36. After that, thecleaning device 20 counts the totalizing time T1 of the detected binarized waveform in the normal determination time (Step S110). The count of the totalizing time T1 is executed by thedetermination unit 39 to which the binarized waveform is input. - Then, the
cleaning device 20 determines whether the normal determination time has passed (Step S112). This determination is made by thedetermination unit 39. When the normal determination time has not passed (Step S112: No), thecleaning device 20 returns the process control to Step S110 and repeats the count of the totalizing time T1. When the normal determination time has passed (Step S112: Yes), thecleaning device 20 counts the totalizing time T2 of the detected binarized waveform in the clogging determination time (Step S114). The count of the totalizing time T2 is executed by thedetermination unit 39 to which the binarized waveform is input. - Next, the
cleaning device 20 determines whether the clogging determination time has passed (Step S116). This determination is made by thedetermination unit 39. When the clogging determination time has not passed (Step S116: No), thecleaning device 20 returns the process control to Step S114 and repeats the count of the totalizing time T2. - When the clogging determination time has passed (Step S116: Yes), the
cleaning device 20 determines whether the totalizing time T2 is not less than the totalizing time T1 (Step S118). This determination is executed by the comparingcircuit 39 g of thedetermination unit 39. As a determination result, when the totalizing time T2 is less than the totalizing time T1, the B/F cleaning liquid flows through thepipe 31 within the normal determination time and thesuction nozzle 21 b is not clogged. Therefore, thecleaning device 20 terminates the clogging detection of thesuction nozzle 21 b. - In contrast, when the totalizing time T2 is not less than the totalizing time T1, the B/F cleaning liquid flows through the
pipe 31 in the clogging determination time that is after the normal determination time. Thus, thecleaning device 20 determines that thesuction nozzle 21 b is clogged (Step S120). Therefore, thecleaning device 20 stops discharging the B/F cleaning liquid to thereaction vessel 7 a (Step S122), and terminates the clogging detection of thesuction nozzle 21 b. Thecleaning device 20 then causes theoutput unit 43 of theautomatic analyzer 1 to display a warning such as the effect that thesuction nozzle 21 b is clogged or the requirement of maintenance. - When the cleaning operation of the
suction nozzle 21 b in thecleaning tank 30 is terminated, thenozzle transferring unit 22 of thecleaning device 20 returns the plurality of B/Fcleaning nozzle pairs 21A to 21F to the position of thereaction vessel 7 a of the reaction table 7 to start sucking the reaction liquid within thereaction vessel 7 a. If the B/F cleaning liquid is discharged to thereaction vessel 7 a when thesuction nozzle 21 b is clogged, thesuction nozzle 21 b cannot suck the reaction liquid within thereaction vessel 7 a and thus the B/F cleaning liquid overflows from thereaction vessel 7 a. Therefore, thecleaning device 20 stops discharging the B/F cleaning liquid to thereaction vessel 7 a. - As described, the
cleaning device 20 detects the change of electrostatic capacity between thesuction nozzle 21 b and thereservoir electrode 33 a as a binarized waveform that is the difference relative to a threshold voltage, and determines whether thesuction nozzle 21 b is clogged based on the totalizing times T1 and T2 of the binarized waveform in the normal determination time and the clogging determination time. The reaction liquid sucked by thesuction nozzle 21 b during B/F cleaning has a large fluctuation range of an electrostatic capacity, whereas the B/F cleaning liquid is stable because of a small fluctuation range of an electrostatic capacity. Thus, it is preferable to use the B/F cleaning liquid in terms of the detection precision of electrostatic capacity or the accuracy of detection. - The
cleaning device 20 detects whether thesuction nozzle 21 b is clogged based on the change of electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 between thesuction nozzle 21 b and thereservoir electrode 33 a of thereservoir 33. Thecleaning device 20 may alternatively detect whether thesuction nozzle 21 b is clogged based on the change of electrostatic capacity caused by the B/F cleaning liquid flowing through at least one of thepipe 31 between thesuction nozzle 21 b and thedetection electrode 32 and thepipe 31 between thedetection electrode 32 and thereservoir electrode 33 a of thereservoir 33. -
FIG. 14 illustrates examples of the voltage variation, the threshold voltage, and the binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 based on the change of electrostatic capacity caused by the B/F cleaning liquid flowing through thepipe 31 between thesuction nozzle 21 b and thedetection electrode 32 when thesuction nozzle 21 b is not clogged with foreign materials.FIG. 14 also indicates the normal determination time and the clogging determination time. - In contrast,
FIG. 15 illustrates examples of the voltage variation, the threshold voltage, and the binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 in the normal determination time and the clogging determination time when thesuction nozzle 21 b is partially clogged. When thesuction nozzle 21 b is perfectly clogged, the voltage variation, the threshold voltage, and the binarized waveform output from thedifferential amplifier 36 j of the detectingunit 36 in the normal determination time and the clogging determination time are as illustratedFIG. 12 . - The
cleaning device 20 can determine whether thesuction nozzle 21 b is clogged by comparing the totalizing time T1 of the binarized waveform in the normal determination time with the totalizing time T2 of the binarized waveform in the clogging determination time that are calculated based on the change of electrostatic capacity between thesuction nozzle 21 b and thedetection electrode 32. Similarly, thecleaning device 20 can detect whether thesuction nozzle 21 b is clogged based on the change of electrostatic capacity between thedetection electrode 32 and thereservoir electrode 33 a of thereservoir 33. - It is preferable that the
cleaning device 20 detects whether thesuction nozzle 21 b is clogged based on the change of electrostatic capacity between thesuction nozzle 21 b and thereservoir electrode 33 a of thereservoir 33 because the flow of the B/F cleaning liquid can be checked over the entire length of thepipe 31. However, it is advantageous that thecleaning device 20 detects whether thesuction nozzle 21 b is clogged based on the change of electrostatic capacity between thesuction nozzle 21 b and thedetection electrode 32 because the clogging of thesuction nozzle 21 b can be quickly detected. - The
cleaning device 20 can detect whether thesuction nozzle 21 b is clogged, using the time at which the binarized waveform becomes an ON state in the normal determination time illustrated inFIG. 10 as a standard and measuring the delay of the binarized waveform that is the time difference (ΔT) illustrated inFIG. 11 between the time and the time at which the binarized waveform becomes an ON state in the clogging determination time by thefirst timer 39 e and thesecond timer 39 f. In this case, the occurrence of temporal clogging of thesuction nozzle 21 b and thepipe 31 can be known using the length of the measured time difference (ΔT). If a relationship between the time at which the binarized waveform becomes an ON state in the determination time and the temporal clogging state of thesuction nozzle 21 b and thepipe 31 is previously checked and is recorded in thestorage unit 44, theautomatic analyzer 1 can automatically and previously notice the requirement of maintenance related to the B/Fcleaning nozzle pairs 21A to 21F and thepipe 31 using thecontrol unit 45. - In the cleaning period illustrated in
FIG. 5 , the transfer time and stop time of the B/F cleaning nozzle pairs performed by thenozzle transferring unit 22, the discharge time of the B/F cleaning liquid performed by thedischarge nozzle 21 a, and the opening time of thesuction valve 34 and the opening time of theexhaust valve 35 can be appropriately changed in accordance with the B/F cleaning situation in thereaction vessel 7 a and the cleaning situation of thesuction nozzle 21 b in thecleaning tank 30. - In the embodiment, only the normal determination time and clogging determination time are set. However, a gray zone time may be provided between the normal determination time and the clogging determination time so as to previously notice the maintenance of the B/F
cleaning nozzle pairs 21A to 21F and thepipe 31. - In the above embodiment, the cleaning device, the method for detecting suction nozzle clogging, and the automatic analyzer that are used for an immunological test are described. However, the present invention can be used in the cleaning device, the method for detecting suction nozzle clogging, and the automatic analyzer that are used for a biochemical test or a gene test.
- The configuration of the detecting
unit 36 is not limited to that illustrated inFIG. 3 as far as it can detect the change of electrostatic capacity between thesuction nozzle 21 b and thereservoir electrode 33 a as a binarized waveform that is the difference relative to a threshold voltage. Furthermore, the configuration of thedetermination control unit 37 is not limited to that illustrated inFIG. 4 as far as it includes the peak-hold-reset output circuit 38 that outputs a peak-hold reset signal to the peak-hold circuit 36 i of the detectingunit 36 and thedetermination unit 39 that determines whether each of thesuction nozzles 21 b is clogged based on the binarized waveform input from the detectingunit 36. - Additional advantages and modifications will readily occur to those skilled in the art. Therefore, the invention in its broader aspects is not limited to the specific details and representative embodiments shown and described herein. Accordingly, various modifications may be made without departing from the spirit or scope of the general inventive concept as defined by the appended claims and their equivalents.
Claims (5)
Applications Claiming Priority (1)
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PCT/JP2007/063032 WO2009001463A1 (en) | 2007-06-28 | 2007-06-28 | Cleaning equipment, method for detecting clogging of suction nozzle, and autoanalyzer |
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PCT/JP2007/063032 Continuation WO2009001463A1 (en) | 2007-06-28 | 2007-06-28 | Cleaning equipment, method for detecting clogging of suction nozzle, and autoanalyzer |
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US8894948B2 US8894948B2 (en) | 2014-11-25 |
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US (1) | US8894948B2 (en) |
EP (1) | EP2184610A4 (en) |
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WO (1) | WO2009001463A1 (en) |
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US20120111127A1 (en) * | 2009-09-07 | 2012-05-10 | Shimadzu Corporation | Autosampler |
CN103335920A (en) * | 2013-06-19 | 2013-10-02 | 和承汽车配件(太仓)有限公司 | Plate rubber pipe blocking test machine |
US10527638B2 (en) | 2014-05-13 | 2020-01-07 | Jeol Ltd. | Automated analyzer and nozzle-cleaning method |
EP3517975A4 (en) * | 2016-09-23 | 2020-06-17 | Hitachi High-Tech Corporation | Automated analysis device |
US20200278366A1 (en) * | 2018-03-16 | 2020-09-03 | Hitachi High-Technologies Corporation | Automatic Analysis Device |
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Also Published As
Publication number | Publication date |
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CN101688873B (en) | 2013-04-24 |
EP2184610A1 (en) | 2010-05-12 |
JP4938082B2 (en) | 2012-05-23 |
US8894948B2 (en) | 2014-11-25 |
EP2184610A4 (en) | 2013-04-10 |
JPWO2009001463A1 (en) | 2010-08-26 |
CN101688873A (en) | 2010-03-31 |
WO2009001463A1 (en) | 2008-12-31 |
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